{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:02:20Z","timestamp":1790740940842,"version":"4.1.0"},"reference-count":60,"publisher":"World Scientific Pub Co Pte Lt","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Chin. Med."],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p> Rhein, an anthraquinone drug, is a widely used traditional Chinese medicine. Rhein is a major bioactive metabolite of diacerein which has been approved for treating osteoarthritis with a good safety profile in humans. Gouty arthritis is an inflammatory disease characterized by urate crystal-induced NLRP3 inflammasome activation with up-regulated caspase-1 protease and IL-1[Formula: see text] in macrophages. Inhibition of the NLRP3 inflammasome formation has been considered as a potential therapeutic avenue for treating or preventing many inflammatory diseases. This study aimed to evaluate the anti-inflammatory effects of rhein on gouty arthritis. Rhein within the physiological levels of humans showed no toxicity on the cell viability and differentiation, but significantly decreased the production of IL-1[Formula: see text], TNF-[Formula: see text] and caspase-1 protease in urate crystal-activated macrophages. Compared to medium controls, rhein at the therapeutic concentration (2.5[Formula: see text][Formula: see text]g\/mL) effectively inhibited IL-1[Formula: see text] production by 47% ([Formula: see text]). Rhein did not affect the mRNA levels of CASP1, NLRP3 and ASC, but suppressed the protein expression and enzyme activity of caspase-1. Immunofluorescence confocal microscopy further revealed that rhein suppressed the aggregation of ASC speck and inhibited the formation of NLRP3 inflammasome. Rhein of 5[Formula: see text][Formula: see text]g\/mL significantly decreased the ASC speck to 36% ([Formula: see text]), and reduced the NLRP3 aggregates to 37.5% ([Formula: see text]). Our data demonstrate that rhein possesses pharmacological activity to suppress caspase-1 protease activity and IL-1[Formula: see text] production by interfering with the formation of NLRP3 multiprotein complex. These results suggest that rhein has therapeutic potential for treating NLRP3 inflammasome-mediated diseases such as gouty arthritis. <\/jats:p>","DOI":"10.1142\/s0192415x19500071","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T10:12:01Z","timestamp":1546855921000},"page":"135-151","source":"Crossref","is-referenced-by-count":57,"title":["Rhein, An Anthraquinone Drug, Suppresses the NLRP3 Inflammasome and Macrophage Activation in Urate Crystal-Induced Gouty Inflammation"],"prefix":"10.1142","volume":"47","author":[{"given":"Wan-Chun","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Tzu","family":"Chu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Jian Jan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Keelung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"Twi Biotechnology, Inc., Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Jui","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan"},{"name":"Department of Dermatology, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, College of Medicine and Chang Gung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Der-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Center, China Medical University Hospital; Department of Medicine, China Medical University, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuen-Iu","family":"Hung","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"219","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"S0192415X19500071BIB001","doi-asserted-by":"publisher","DOI":"10.1002\/art.10709"},{"key":"S0192415X19500071BIB002","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60665-4"},{"key":"S0192415X19500071BIB003","doi-asserted-by":"publisher","DOI":"10.1186\/ar2952"},{"key":"S0192415X19500071BIB004","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-0374"},{"key":"S0192415X19500071BIB005","first-page":"457","volume":"56","author":"Chang W.C.","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"S0192415X19500071BIB006","doi-asserted-by":"publisher","DOI":"10.1038\/srep34533"},{"key":"S0192415X19500071BIB007","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0681"},{"key":"S0192415X19500071BIB008","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205409"},{"key":"S0192415X19500071BIB009","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101405"},{"key":"S0192415X19500071BIB010","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-273417"},{"key":"S0192415X19500071BIB011","first-page":"577","volume":"43","author":"Domagala F.","year":"2006","journal-title":"Biorheology"},{"key":"S0192415X19500071BIB012","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2539::AID-ART434>3.0.CO;2-T"},{"key":"S0192415X19500071BIB013","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.013"},{"key":"S0192415X19500071BIB014","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2011.03.013"},{"key":"S0192415X19500071BIB015","first-page":"CD005117","volume":"2","author":"Fidelix T.S.","year":"2014","journal-title":"Cochrane Database Syst. 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